The BioCD: High-Speed Interferometric Optical Biosensor
The bio-optical compact disc (BioCD) is an optical biochip that uses common-path interferometry on a disc spinning at high speed to detect captured proteins. High-speed scanning moves the detection frequency far from 1/f noise, providing high sensitivity and enabling rapid measurement of high-throughput multiplexed assays. The common-path configuration makes it ultra stable with surface height precision down to 20 pm within the focused probe area. This chapter reviews the state of the art in interferometric detection of proteins using spinning-disc interferometry. There are several common-path configurations that achieve phase quadrature for sensitive detection of surface-immobilized proteins. We have implemented differential phase contrast, in-line, microdiffraction, and adaptive optical approaches. Protein patterning provides spatial frequencies for Fourier-domain detection and spatial multiplexing on the BioCD surface. The detection limits of protein are set by a scaling surface mass density, with a metrology limit below 1 pg/mm. Specific immunoassay applications are described for prostate-specific antigen and haptoglobin. A highly multiplexed platform like the BioCD may enable a Moore's Law of protein detection as the scaling capabilities of protein patterning coevolve with proteomics to explore increasingly complex protein interaction networks.
KeywordsProtein Spot Disc Surface Compact Disc Phase Quadrature Ridge Height
The authors gratefully appreciate all the help and hard work provided by the scientists and engineers at Quadraspec, Inc., and in particular the inspiration and support of Chad Barden.
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